SARS Spike Proteins

thingiverse

In the absence of a known nCoV-Spike protein structure, we identified the surface glycoprotein sequence YP_009724390.1 [1] and characterized it using the AS2TS system [2]. The structures of the Spike proteins from SARS (PDB entries: 5x58 [3], 6nb6 [4], 2dd8 [5], and 3bgf [6]) were identified as the closest and most complete PDB structural templates to use for modeling. These templates provided additional important information about possible complexes with three antibodies: S230, M396, and F26G19. The PDB templates had been experimentally solved at a resolution of 3.2, 4.2, 2.3, and 3.0 Å respectively. We found that the level of sequence identity between nCoV and SARS Spike proteins from the templates is 71%. To assess regions of sequence-structure conservation or variability in the modeled proteins, we created a set of initial structural models using an extensive set of available templates. The comparative analysis between constructed models and all available templates from PDB was performed using the StralSV algorithm [7], which identifies protein fragments that exhibit structural similarities despite low primary amino acid sequence similarity and regions where some structure conformation uncertainties can be observed. Results from these searches were used for modeling of missing loop regions and assessment of possible structure conformation diversity in preliminary models. In the constructed final models, we predicted the conformation of side-chain atoms using SCWRL [8] when residue-residue correspondences did not match. We copied residues that were identical in the template and nCoV-Spike protein from the templates onto the models. The structural and stereochemical quality of the models was checked using a contact-dot algorithm in the MolProbity software package [9], and the final constructed models were finished with relaxation using UCSF Chimera [10]. A set of all provided models was constructed to help assessment of possible different conformations in the Spike – antibody complexes. The value of these structures is that they are computational estimates of how some antibodies with very favorable binding and neutralization properties might interact with the Spike protein from 2019-nCoV virus, when this information cannot be obtained through experimental methods. We used the AS2TS system [2] to identify the surface glycoprotein sequence YP_009724390.1 [1]. The structures of the Spike proteins from SARS (PDB entries: 5x58 [3], 6nb6 [4], 2dd8 [5], and 3bgf [6]) were identified as the closest and most complete PDB structural templates to use for modeling. We found that the level of sequence identity between nCoV and SARS Spike proteins from the templates is 71%. The comparative analysis between constructed models and all available templates from PDB was performed using the StralSV algorithm [7]. Results from these searches were used for modeling of missing loop regions and assessment of possible structure conformation diversity in preliminary models. We predicted the conformation of side-chain atoms using SCWRL [8] when residue-residue correspondences did not match. The structural and stereochemical quality of the models was checked using a contact-dot algorithm in the MolProbity software package [9]. This document was prepared as an account of work sponsored by an agency of the United States government. Neither the United States government nor Lawrence Livermore National Security, LLC makes any warranty, expressed or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights.